A5083865792- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- Nerve injury and regeneration
- Neuroscience and Neuropharmacology Research
- Mechanisms of cancer metastasis
- Protein Kinase Regulation and GTPase Signaling
- Axon Guidance and Neuronal Signaling
- Hereditary Neurological Disorders
- Prion Diseases and Protein Misfolding
- Phagocytosis and Immune Regulation
- RNA Research and Splicing
- Congenital heart defects research
- Neurogenesis and neuroplasticity mechanisms
- RNA regulation and disease
- Memory and Neural Mechanisms
- Cellular Mechanics and Interactions
- Caveolin-1 and cellular processes
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Ion channel regulation and function
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- RNA and protein synthesis mechanisms
Vollum Institute
2018-2019
Oregon Health & Science University
2019
Washington University in St. Louis
2014-2018
NeuroDevelopment Center
2017
Hope Center for Neurological Disorders
2013-2016
City University of New York
2012
College of Staten Island
2011
Adhesion G protein-coupled receptors (aGPCRs) comprise the second largest yet least studied class of GPCR superfamily. aGPCRs are involved in many developmental processes and immune synaptic functions, but mode their signal transduction is unclear. Here, we show that a short peptide sequence (termed Stachel sequence) within ectodomain two (GPR126 GPR133) functions as tethered agonist. Upon structural changes receptor ectodomain, this intramolecular agonist exposed to seven-transmembrane...
The myelin sheath surrounding axons ensures that nerve impulses travel quickly and efficiently, allowing for the proper function of vertebrate nervous system. We previously showed adhesion G-protein-coupled receptor (aGPCR) Gpr126 is essential peripheral system myelination, although molecular mechanisms by which functions were incompletely understood. aGPCRs are a significantly understudied protein class, it was unknown whether couples to G-proteins. Here, we analyze Dhh(Cre);Gpr126(fl/fl)...
Abstract Mutations in GPR56 , a member of the adhesion G protein-coupled receptor family, cause human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Magnetic resonance imaging (MRI) BFPP brains reveals myelination defects addition to malformation. However, cellular role oligodendrocyte development remains unknown. Here, we demonstrate that loss Gpr56 leads hypomyelination central nervous system mice. levels are abundant throughout early stages development, but...
Significance Adhesion G protein-coupled receptors (GPCRs) are expressed in many developing organs, immune cells, and cancer suggesting that they might play an important role physiological pathological functions. Compared with their potential importance, function signaling mechanisms poorly understood. Disruption of the receptor 126 ( Gpr126 ) gene mice leads to lack myelination peripheral nervous system (PNS) heart abnormalities. Similarly, zebrafish mutant line gpr126 st49 exhibits PNS...
Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes incompletely understood. We previously showed that adhesion G protein-coupled receptor Gpr126/Adgrg6 is SC myelination. Interestingly, expression of Gpr126 maintained in adult SCs, suggestive a function mature nerve. therefore investigated role repair by studying an inducible SC-specific knock-out mouse model. Here, we show remyelination severely delayed...
Myelin is a multilamellar sheath generated by specialized glia called Schwann cells (SCs) in the peripheral nervous system (PNS), which serves to protect and insulate axons for rapid neuronal signaling. In zebrafish rodent models, we identify GPR56/ADGRG1 as conserved regulator of PNS development health. We demonstrate that, during SC development, GPR56-dependent RhoA signaling promotes timely radial sorting axons. mature PNS, GPR56 localized distinct cytoplasmic domains, required establish...
The molecule responsible for the enzyme activity plasma membrane (PM) aminophospholipid translocase (APLT), which catalyzes phosphatidylserine (PS) translocation from outer to inner leaflet of membrane, is unknown in mammals. A Caenorhabditis elegans study has shown that ablation transbilayer amphipath transporter-1 (TAT-1), an ortholog a mammalian P-type ATPase, Atp8a1, causes PS externalization germ cells. We demonstrate here hippocampal cells dentate gyrus, and Cornu Ammonis (CA1, CA3)...
Aberrant expression of the presynaptic serotonin 1A receptor (5-HT1A-R) because a polymorphism in 5-HT1A-R gene is associated with severe depression human, whereas its absence up to postnatal day 21 (P21) forebrain mice results heightened anxiety adulthood. These observations collectively indicate that has crucial role brain development. To understand mechanistic underpinnings this phenomenon, we used organotypic slice cultures hippocampi from C57BL6 (C57) at P15, which coincides peak...
Localized translation in neurites helps regulate synaptic strength and development. Dysregulation of local is associated with many neurological disorders. However, due to technical limitations, study this phenomenon has largely been limited brain regions laminar organization dendrites such as the hippocampus or cerebellum. It not examined cortex, a region importance for most disorders, where each neuronal population are densely intermingled cell bodies others. Therefore, we have developed...
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and extracellular matrix to first sort ensheathe a single then myelinate it. Neuregulin 1 type III (Nrg1III) laminin α2β1γ1 (Lm211) are key axonal signals, respectively, but how their signaling integrated if each molecule controls both sorting myelination unclear. Here, we use series of epistasis experiments show that Lm211 modulates neuregulin ensure correct...
Abstract In the central nervous system (CNS), oligodendrocytes myelinate multiple axons; in peripheral (PNS), Schwann cells (SCs) a single axon. Why are myelinating potentials of these glia so fundamentally different? Here, we find that loss Fbxw7 , an E3 ubiquitin ligase component, enhances potential SCs. mutant SCs make thicker myelin sheaths and sometimes appear to axons fashion reminiscent oligodendrocytes. Several phenotypes due dysregulation mTOR; however, remarkable ability ensheathe...
The class of adhesion G protein–coupled receptors (aGPCRs), with 33 human homologs, is the second largest family GPCRs. In addition to a seven‐transmembrane α‐helix—a structural feature all GPCRs—the aGPCRs characterized by presence large N‐terminal extracellular region. addition, but one (GPR123) contain GPCR autoproteolysis–inducing (GAIN) domain that mediates autoproteolytic cleavage at autoproteolysis site motif generate N‐ and C‐terminal fragments (NTF CTF, respectively) during protein...
Abstract The adhesion class of G protein–coupled receptors (GPCRs) is the second largest family GPCRs (33 members in humans). Adhesion (aGPCRs) are defined by a large extracellular N‐terminal region that linked to C‐terminal seven transmembrane (7TM) domain via GPCR‐autoproteolysis inducing (GAIN) containing GPCR proteolytic site (GPS). Most aGPCRs undergo autoproteolysis at GPS motif, but cleaved fragments stay closely associated, with fragment (NTF) bound 7TM (CTF). NTFs most contain...
Abstract The mechanistic target of rapamycin complex 1 (mTORC1) is known to regulate cellular growth pathways, and its genetic activation sufficient enhance regenerative axon following injury the central or peripheral nervous systems. However, excess mTORC1 may promote innervation defects, activity mediates injury-induced hypersensitivity, reducing enthusiasm for pathway as a therapeutic target. While required full expression some pain modalities, effects on nociceptor phenotypes sensory...